Epstein-Barr virus is one of a limited number of viruses associated with human cancers. The ability of EBV to transform primary B lymphocytes and establish a latent infection is a prerequisite to any EBV-associated malignancy. Our long-term objective is to identify the cellular pathways targeted by EBNA-3C that mediate its essential role in EBV-induced transformation. Specifically, we propose to: 1. Identify the mechanisms of transcriptional activation by EBNA-3C. 2. Determine the significance of EBNA-3C function within the context of EBV contributes to EBNA-3C's essential role in EBV-mediated transformation. We will evaluate the significance of those EBNA-3C functions that we have already identified, those identified in this proposal, as well as domains that have been conserved during evolution of human and primate viruses, by examining the ability of mutant EBNA-3C proteins to function transformations. 3.Identify cellular genes regulated by EBNA-3C. EBNA-3c is likely to regulate expression cellular genes that contribute to EBV-mediated transformation. EBNA-3C-regulated genes will be identified by examining pathways EBNA-3C is known to target as well as by representational difference analysis. Characterization of these genes is likely to identify cellular effectors of EBNA-3C function. The proposed experiments will enable us to determine the cellular pathways targeted by EBNA-3C and thus its unique contribution to EBV-mediated transformation. Analysis of these pathways using EBNA-3C as a probe, is highly likely to not only further our understanding of EBV-associated malignancies, but also increase our knowledge of the control of cellular proliferation that may be disrupted in other types of cancers.